This NIH shared instrument request is the key component in establishing a unique facility for hyperpolarized nuclear magnetic resonance (NMR) spectroscopy that provides a dramatic 10,000+fold improvement in sensitivity for investigating metabolic pathways and MR imaging biomarker discovery for a variety of human diseases. Funds are requested for the core component of this facility: an Oxford Instruments Biotools HyperSenseTM Dynamic Nuclear Polarizer (DNP), which is a new product first offered in the last year. This system will be combined with two existing high field 500 MHz vertical bore NMR spectrometers located in the UCSF NMR lab on the Mission Bay campus. Both magnets are dedicated to running biomedical samples and they have complimentary features, including high-resolution magic angle spinning (HR-MAS) spectroscopy capabilities, and a cryoprobe with an automatic sample changer. The UCSF NMR lab and associated research laboratory contain all of the pathology, chemistry and molecular analysis equipment required to prepare 13C labeled substrates for polarization and to correlate metabolic profiles with pathologic, genetic and protein changes for biomarker discovery. This proposal will take advantage of these extensive University of California and NIH funded resources. The unprecedented increase in sensitivity obtained from DNP polarization will permit NMR measurements previously considered impossible for studying human and animal tissue, biofluids, and pre-clinical cell and tissue culture models. Increased sensitivity will also reduce the time required for performing 1-D and 2-D NMR studies of tissues and cells. The coupling of DNP technology with high resolution NMR spectroscopy will allow the investigation of numerous hyperpolarized 13C labeled substrates, optimize their polarization and optimize the acquisition of the hyperpolarized spectroscopic data in a cost effective manner. This new facility is critical for not only developing applications that take advantage of the DNP technology in tissues and cells but also for translating the insights gained in these model systems into the ongoing pre-clinical animal and eventually clinical hyperpolarized 13C spectroscopic imaging studies being conducted at UCSF. [unreadable] [unreadable] This combination of high field NMR spectrometers with a HyperSenseTM DNP polarizer will be coupled with the large number of successful NIH-funded MR imaging research programs at UCSF and will create a unique hyperpolarized MR program that will greatly advance our understanding of the metabolism for a wide variety of diseases and result in the identification of new metabolic biomarkers of disease presence, aggressiveness and therapeutic response. [unreadable] [unreadable] [unreadable]